Preparations of medicinal substances and method of making the same



To all whom it may concern:

i ii

JACOB WERSHOW, OF NEW HAVEN, CONNECTICUT.

JPREPARETIONS OF MEDICINAL SUBSTANCES AND METHOD OF MAKING THE SAME.

No Drawing.

Be it known that- I, JACOB WERSHOW, a citizen of the United States, and resident of New Haven, in the county of New Haven and State of Connecticut, have invented certain new and useful Improvements in Preparations of Medicinal Substances and Methods of Making the Same, of which the following is a specification.

My present invention relates more particularly to preparations of aspirin and the primary object is to embody characteristic medicinal roperties of aspirin, in non-solid form, pre erably in the form of a relatively fluid or nonviscous liquid.

At the present time the medicinal properties of aspirin are well known and its commercial production and use in relatively enormous quantities has been practlcally standardized in the form of so-called aspirin tablets. The aspirin employed is the acid form known as acetyl-salicylic acid, formula,

c, coon.

' This substance is a crystalline solid and the tablets comprise the pulverized aspirin com bined and compressed with a suitable binder and filler material. This standardized commercial practice has resulted from the fact that the acid aspirin is insoluble, or practically insoluble in all ordinary liquids of the kinds which are suitable for use without themselves producing destructive or harmful chemical or medicinal effects when taken internally. These aspirin tablets, however, are objectionable because, on account of their size and dryness, swallowing them whole is difficult and for some people impossible; also because the filling and binding material or materials are apt to have more or less objectionable physiological effects, particularly in cases where the stomach is in a sensitive or disturbed condition; also because the time required for the solid aspirin to be completely freed from the binder and to be released in the system in Specification of Letters Patent.

Application filed. February 11, 192}. Serial No. 444,278.

tities required to produce the desired mediclnal effect of the aspirin without any objectionablc effects resulting from the liquid vehicle itself, which permits instant freeing of the aspirin medicinal principle from the liquid vehicle, and which presents said medlcinal principle to the action of the stomach, in already liquid form.

The preferred source from which the aspirin medicinal principle is derived is preferably ordinary commercial aspirin which, as is well known, embodies the aspirin medicinal principle in the form of a relatively stable, solid compound having an acid reactlon and which is insoluble or only slightly soluble in any of the liquid vehicles ordinarily employed for medicinal purposes. As an lmportant constituent of the liquid vehicle,

1 preferably employ glycerine which may be the standard commercial product containing the usual percentage of water, but in the finished product the glycerine may be and preferably is still further diluted by certain appropriate liquids, preferably of agreeable taste, as for instance, the ordinary standard syrup of cane sugar, which, if desired, may be diluted with water and alcohol and suitably 'flavored as with spirit of Wintergreen, as in standard aromatic elixir. One purpose of such dilution is to decrease the amount of glycerine practically necessary for serving the function of vehicle, and one feature of my invention consists in the discovery that the dilution of the glycerine .may be carried to a pointwhere the amount of glycerine in ordinary doses, (equivalent to an ordinary five grain aspirin tablet), will be toosmall to produce the demulcent or relaxing effects which are characteristic of glycerine when used in larger doses. In producing the preferred product, the standard aromatic elixir or its equivalent has a further function which will be explained below. The precise composition of standard aromatic elixir may be found by reference t the text books, but it may be well to note here that it comprises approximately equal parts of saturated solution of cane sugar, alcohol and water with a little purified talc and a small amount of flavoring material, such as spirit of wintergreen. Other diluents may be used and-in certain cases glycol may be used as a substitute for or in combination with glycerine.

The ordinary acid aspirin of commerce,

however, is not soluble in glycerine, and my invention contemplates the employment of acid aspirin, together with the further propcity of being soluble in the glycerine even though the latter be diluted for the purposes above described.

A desirable but more specific feature of mydainv'ention consists in combining with the aspirin solution one or more other medicinal agents, one preferably in the nature of a physio and the other preferably in the nature of a tonic or stimulant; and one feature of my invention includes the investigation and discovery of desirable medicinal substances of both these classes capable of I use in conjunction with the liquid vehicle,

the aspirin principle and with each other which are without deleterious chemical or physiological reactions either by the process of compounding or subsequent lapse of time or by stomach or other reactions after administering to the patient. 7 a

The preferred laxative is aloin, the active principle of bitter aloes, this being easily incorporated in the final product without being objectionably affected by, pr itself producing objectionable effects on the other constituents.

The'stimulant or tonic element is preferably elixir of lactated-pepsin, a suitable ercentage of which may be added to the nal product and which, when employed, will constitute the mixture a mild but active stimulant, notwithstandingthe fact that a limited percentage of glycerine is incorporated in the preparation;

While my invention is not limited to the employment of all the above constituents and while the stimulant and physic principle may be varied or omitted, if desired, nevertheless, obtaining the best balanced medicinal effect of the aspirin principle in conjunction with the other medicinal agents, will depend to a considerable extent on the proportion of the various substances and the methods by which they are associated, and while these may be varied within quite wide limits, the following is illustrative of a desirable way of producing a product which I have long tested and have found to result in a preparation which is superior to ordinary aspirin tabletsas an agency for applying the active principle of the aspirin as a medicine, besides being in li uid form and having all of the advantages rst above mentioned.

Dissolve the bicarbonate of soda in the alcohol water'bonstituent, preferably the aromatic elixir, the quantities being proportioned so as to make a strong and preferably saturated or nearly saturated solution of the bicarbonate, then add an equal or somewhat greater quantity of commercial glycerine, then gradually but not too slowly add the commercial aspirin, preferably pulverized, stirring it in thoroughly and if desired warming the mixture, but not to exceed say 50 centigrade. aspirin is by weight slightly more than twice the amount of the bicarbonate of soda. This will result in diffusing the aspirin'principle in soluble form throughout the liquid. If the primary bicarbonate solution is approximately saturated the resulting aspirln solution will be strong enough so that a level teaspoonful of the product will constitute a good dose, comparable to that of an ordinary aspirin tablet. Of course the solution may be further diluted, if desired.

/If aloin is to be used it may be mixed in the water with a small additional quantity of liquid, as for instance the aromatic elixir, which may be then added to(the aspirin preparation. A stimulant such as elixir of lactated-pepsin may be added to the aspirin preparation either with or without the aloin; and either before or after addition of the latter.

A more specific description of desirable proportions is as follows To make about a pint of the product dissolve =3 oz. of bicarbonate of soda in say 6 oz. to 7 oz. of the aromatic elixir, and then add say 8 oz., that is about one-half pint of commercial glycerine. This amount of bicarbonate will take care of say 1% oz. of commercial aspirin. After the aspirin has been incorporated, add enough aromatic elixir to make up the full pint and if aloin is to be employed a small quantity say about 16 grains may-be mixed in a mortar with the additional aromatic elixir before adding it to the liquid aspirin preparation.

While wide variations from the aboye are possible, excess of either bicarbonate of soda or of undissolved aspirin may be avoided by sticking fairly close to the ratio of 71% aspirin to 29% bicarbonate of soda. Obviously the soluble-salt of aspirin may be produced and combined with the liquid vehicle in other. ways.

In the specific illustration last above given it will be noted that the total weight of the product is approximately 18 oz. andv that-the commercial aspirin used being 1?; oz., roughly stated, is somewhere around 7% of the total. The characteristic aspirin The amount of or the alcohol or the eonora groups in the aspirin salt being approximately the same in number as in the acid aspirin, it will be seen that 7% represents a close approximation of the 'efi'ective aspirin strength of, the product. It is obvious that a product of somewhat greater strength might be used and that it would still be useful if the aspirin percentage were reduced to 2% or even 1%.

In the preferred preparation where flavoring extract is employed it is preferably the, alcoholic extract, and in such case, the "alcohol, though amounting only to say of a teaspoonfulper dose, is in the nature of a stimulant tending to countervale any small medicinal effects or tendencies of the half teaspoonful or less glycerine with which it is mixed.

Where a flavoring is afforded by aromatic elixir containing alcohol the same thing is true. Where aloin is used with or without the alcoholic content, which would be atforded by aromatic elixir, the proportions are preferably such that the amount of'mix ture required for a standard dose of aspirin includes only very small doses of the aloin glycerine. I claim l. A medicinal aspirin pre aration comprising a'spirin rendered solu leb a solution of acid bicarbonate of an alkaline metal dissolved in a li uid containing alcohol; and uniformly di usedthrou bout, a composite liquid vehicle comprising said first-- mentioned liquid mixed with and serving as'a diluent for a liquid of the glycerineglycol type.

2. A medicinal aspirin preparation made from acid aspirin rendered soluble by an approximately! saturated solution of acid bicarbonate of soda dissolved in aromatic elixir and mixed with a large percentage of glycerine.

3. A medicinal aspirin reparation comprising a desired weight 0 aspirin rendered soluble by less than half its weight of hicarbonate of soda dissolved in a medicinally harmless liquid of sufficient quantity to render the bicarbonate solution approximately saturated; and uniforml diffused throughout a mixture of said liquid with an approxlmately similaramount of glycerine.

a. A medicinal aspirin preparation con taining approximately" one part each of water, alcohol and syrup mixed with approxlmatel three parts lycerine, and havmg an a alme salt 0 aspirin dissolved therein.

5. An aspirin preparation comprising a liquid solutioncontaining glycerine and a diluent, and, in solution therein, a soluble aspirin salt to an amount which is by weight and predetermined by the amount of bi-. carbonate available for rendering it soluble.

7 The method of making a liquid preparation of aspirin, which method conslsts= in rendering acid aspirin soluble by action ofa solution of acid bicarbonate of an alkaline metal in the presence of glycerine serving as a solvent forthe resulting soluble aspirin compound.

8. The method of making a liquid preparation of aspirin, which method consists in rendering acid aspirin soluble by action of a solution of bicarbonate of an alkaline metal in the presence of another, liquid serving as a solvent for the resulting soluble aspirin compound.

9. A medicinal aspirin preparation comprising soluble aspirm, glycerine and aloin in such pro ortions that a standard dose of aspirin 1nc udes only very small doses of 'glyc'erine and aloin.

10. A medicinal aspirin preparation comprising soluble aspirin, glycerine, alcohol and aloin in such proportions that a standard dose of aspirin includes only very small doses of glycerine, alcohol and aloin.

11. A llquid, medicinal aspirin containing the products resulting from reaction with aspirin of-carbonate of an alkalinemetal. or alkaline earth in solution; including the liquid of the solution-and the salt of aspirin formed as a product of the reaction; all in presence of and with another medicmally unobjectionable liquid in which saidsalt of aspirin is dissolved. v 4

12. A liquid medicinal aspirincontainm the, products resulting from action of aci aspirin with two medicm'ally' harmless JACOB wnasnow.

said soluble 

